i) Field of the Invention
The invention relates to a method of myogenesis and/or angiogenesis in a heart, including revascularization an ischemic myocardium, and to a device for myogenesis and/or angiogenesis, including revascularizing of an ischemic myocardium.
ii) Description of Prior Art
Transmyocardial laser revascularization (TMLR) has been employed in clinical trials to reduce angina. This laser technology was developed in the belief that channels formed in the myocardium by the laser would provide a replacement vascular system.
It has now been found that the laser channels do not remain intact; although increased vascular density is maintained. It has now been found that contrary to the original hypothesis of a laser channel serving as a conduit for new blood flow from the ventricular cavity to the myocardium, the physiological basis of TMLR appears to be angiogenesis caused by non-specific tissue damage.
The laser technology has the disadvantage that it is costly, the equipment currently (1999) having a cost of the order of $250,000 to 350,000 (U.S.), and requires sophisticated monitoring for its safe use.
Angiogenesis is employed to treat an ischemic myocardium employing angiogenesis provoking agents.
Myogenesis is employed to treat a failing myocardium such as by administration of growth factors.
It is an object of the invention to provide a new method of revascularization on ischemic myocardium.
It is another object of the invention to provide a new device for revascularizing an ischemic myocardium.
A further object of the invention is to provide a method of myogenesis and/or angiogenesis in a failing heart.
A still further object of the invention is to provide a device for myogenesis and/or angiogenesis in a heart.
In accordance with one aspect of the invention, there is provided a transthoracic method of angiogenesis or myogenesis of a myocardium comprising: puncturing a myocardium, from epicardium to endocardium, simultaneously, at a plurality of spaced apart sites, with a plurality of needles, and simultaneously withdrawing the plurality of needles from the punctured myocardium.
In accordance with another aspect of the invention there is provided a device for transthoracic angiogenesis or myogenesis of a myocardium comprising: a support member dimensioned for insertion into proximity with a myocardium, a plurality of needles supported by said support member in spaced apart relationship, said needles being effective to puncture a myocardium from epicardium to endocardium.
The invention has particular application in angiogenesis for the revascularization of an ischemic myocardium, but also has application in myogenesis in the treatment of a failing heart.
In accordance with the invention it has been determined that a tissue injury-induced angiogenesis is provided in an ischemic myocardium employing needle puncture instead of laser technology.
The device of the invention has a plurality of needles which are supported, in spaced apart relationship, by a support member.
Suitably the needles extend from a face of the support member which typically will be a flat face, but might have other contours, such as a concavely curved face. Typically the needles will be in generally parallel relationship and conveniently will extend perpendicularly of a flat support face. Conveniently the device has 5 to 15, preferably about 10 needles, extending in parallel relationship from the support face.
The needles are suitably spaced apart such that adjacent needles are spaced with their central axes, 2 to 4 mm apart.
Each needle should have a length permitting a puncture in the myocardium extending from the epicardium to the endocardium. This puncture depth will vary in individual patients but generally the puncture depth will be 6 to 20 mm, more usually 8 to 15 mm. The needles have a length necessary to meet the desired depth of penetration. In use the surgeon will typically have access to a plurality of devices of the invention, which may differ in the lengths of the needles, so that a particular length can be selected based on the patient and the desired depth of penetration.
The needle should have a maximum diameter of at least 1.25 mm and generally 1.25 to 1.8 mm to provide a puncture of adequate transverse dimension to provide a wound for the purpose of the invention. The wound or injury to the myocardium caused by the punctures with the needles in the device of the invention causes an increase in perfusion.
The reference to xe2x80x9cmaximumxe2x80x9d diameter here in contemplates the diameter of the body of the needle as distinct from the point and adjacent portions, since the body will taper to the point, in a short region adjacent the point. Furthermore the reference to xe2x80x9cdiameterxe2x80x9d is not intended to be construed as limiting the needles to being of circular cross-section, and xe2x80x9cdiameterxe2x80x9d in reference to the needles is to be understood as identifying the major cross-sectional dimension of the needles. Preferably, however, the needles will have a circular or substantially circular cross-section.
It will be understood that a single device of the invention may be employed to provide more than one cluster of punctures, such as by puncturing adjacent zones of the myocardium with the same device to provide a desired area of punctures.
By selecting a device of the invention of appropriate physical parameters with respect to needle dimensions, and number of needles, the surgeon can control both the puncture density and depth as required based on the needs of individual patients. Furthermore the employment of the simultaneous puncturing of the invention, shortens and simplifies the surgical procedure, with the consequent benefit to the patient.
Depending on the mode of use or route of deployment the needles may be fully exposed at all time, for example, in a conventional sternotomy; or the needles may be temporarily shielded prior to and following the puncturing to avoid damage to adjacent members during the introduction of the device to the region of the myocardium. Thus, if employed in key hole surgery, the device is fed through a port into the chest cavity and the needles are temporarily shielded during the feeding.
In a particular embodiment in which the needles are to be temporarily shielded, there is additionally included a shield, the shield and support member being integrally connected and at least one of the shield and support member is movable relative to the other from a first position in which the needles are concealed, in a non-puncturing configuration, by the shield, to a second position in which the needles are exposed for puncturing. In the first position in which the needles are in the non-puncturing configuration the support member can be readily inserted into the chest cavity such as by minimally invasive thoracotomy, without danger of the needles inadvertently injuring tissue during the insertion into the chest cavity.
In use the support member, with the needles concealed, is brought into close proximity with the heart, for example, an ischemic myocardium, and the needles are exposed to puncture the heart, for example, the ischemic myocardium by adjusting the support member to the second position. In one embodiment a shield face of the shield has orifices therethrough aligned with the needles, and the support member and needles are displaceable relative to the shield face so that the needles extend through the orifice to the exposed second position.
On completion of the required puncturing of the ischemic myocardium, the needles are withdrawn to the concealed configuration such as by displacing the support member relative to the shield face of the shield so that the needles are retracted through the orifices, and the device can be withdrawn from the chest cavity.
In a further preferred embodiment conduits extend through all or some of the needles, each conduit having an inlet and an outlet. Each inlet communicates with a hollow supply zone in the interior of the support member, for supply of an agent such as an exogeneous angiogenic factor or drug; each outlet is at the needle point. In this way a desired angiogenic factor or factors can be injected at the puncture sites of the ischemic myocardium. It is found that such factors enhance the revascularization.
Suitable angiogenic factors include VEGF (vascular endothelial growth factor).
The device can also be employed to deliver other agents at the puncture sites for myogenesis or angiogenesis, including implanting of myoblasts or stem cells to grow new muscles, and cardiomyocyte precursor cells.
A particular advantage of the invention is that the device can be employed with minimally invasive surgery; but the method employing the device, can also be carried out with open chest surgery or conventional sternotomy.
Minimally invasive techniques which can be employed include introducing the device transthoracically or. The device could also be introduced through a left thoracotomy incision which is an opening between the ribs of the patient, or it could be done thoracoscopically through the use of three small incisions where the device would be introduced into the chest cavity.
In the sternotomy approach the device could be applied to the heart in conjunction with conventional coronary artery bypass surgery. The device used at this stage would not necessarily need any protective shield as it is being used directly onto the heart with complete exposure and safety. The device could be similar to that as is described below in FIGS. 1A-1C. In addition, a similar type of device could be used through the thoracotomy which again gives direct and open access to the ischemic myocardium. In using the device through a thoracoscope which is the use of three small incisions on the left side of the chest cavity, the device would be such that it slides within a shield as described below, positioned appropriately to the area of the ischemic myocardium, allowed to open much like an umbrella and then pierce the myocardium. This device could be withdrawn within the protective covering of the shield and then withdrawn completely outside of the chest.
The device might also be introduced by percutaneous access through the femoral artery, in this case the device is passed up through the femoral artery into the aorta down through the aortic valve and into the left ventricle cavity as is done during cardiac catheterization. A protective sleeve follows the device into the left ventricular cavity and the device is then pushed out through the sleeve, opens up like an umbrella and is allowed to press up against the left ventricular cavity creating the punctures using the needles. The needles are removed by bringing them back into the protective sheath and then withdrawing the sheath and device completely out of the femoral artery. Entry to the femoral artery may be through standard femoral artery sheaths which are used during cardiac catheterization.
On the other hand there are disadvantages in such percutaneous access, and the present invention overcomes such disadvantages. In particular, coronary arteries are at the surface of the heart (epicardial) and thus when external punctures are formed as in the transthoracic method of the invention, the surgeon is able to view the coronary arteries, and avoid puncturing them. Employing percutaneous access, on the other hand, results in the punctures being formed from internally of the heart, towards the exterior; in this approach the coronary arteries cannot be seen by the surgeon. If the coronary arteries are inadvertently punctured from the interior of the heart, massive myocardial infarctions i.e. heart attack may occur which can result in immediate death of the patient. In addition traversing the entire myocardium from the endocardium to the epicardium might result in external bleeding around the heart and cause cardiac compression. The use of percutaneous access thus necessitates employment of complex equipment to determine at all times the relative locations of the needles and the coronary arteries, so as to minimize the potential for inadvertently puncturing the coronary arteries.
If used in key hole surgery the device slides through a port into the chest cavity with needles protected by a shield or sleeve as outlined hereinbefore. When the position of the heart is determined, the needles are exposed such as by adjustment of their position relative to the shield member. Suitably the support member for the needles may have a flexible hinge at its centre such that the support member can move at a 90xc2x0 angle in one geometric plane. In this way the support member may be concealed within the protective shield during passage in and out of the chest cavity. At the site of employment the needles are exposed and the support member flexes 90xc2x0 such that the needles point directly at the heart. Suitably the device will have a spring handle permitting for control of depth or puncture penetration.
The use of hollow needles allows for delivery of agents, for example, angiogenic and myogenic factors.
Finally the device can be introduced through a conventional sternotomy which involves cutting open the breast bone as is done in usual coronary artery surgery.